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https://www.readbyqxmd.com/read/29353069/lanthanum-chloride-impairs-memory-in-rats-by-disturbing-the-glutamate-glutamine-cycle-and-over-activating-nmda-receptors
#1
Xiaoyu Hu, Jinghua Yang, Yaling Sun, Xiang Gao, Lijin Zhang, Yingqi Li, Miao Yu, Shiyu Liu, Xiaobo Lu, Cuihong Jin, Shengwen Wu, Yuan Cai
Studies have reported that lanthanum chloride (LaCl3) can across the blood-brain barrier, accumulate in the brain and affect the spatial learning and memory abilities. However, the potential mechanism that LaCl3-induced neurotoxic effects has not yet been defined. Glutamate (Glu) is a vital excitatory neurotransmitter, and the excessive Glu accumulation in extracellular space can induce excitatory neurotoxicity. This study was designed to research the influence of LaCl3 on the spatial learning and memory abilities of rats and to discuss the possible mechanism underlying this effect regarding the extracellular Glu concentration, the Glu-glutamine (Gln) cycle and the N-methyl-D-aspartate (NMDA) receptors...
January 15, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29351585/core-differences-in-synaptic-signaling-between-primary-visual-and-dorsolateral-prefrontal-cortex
#2
Sheng-Tao Yang, Min Wang, Constantinos D Paspalas, Johanna L Crimins, Marcus T Altman, James A Mazer, Amy F T Arnsten
Neurons in primary visual cortex (V1) are more resilient than those in dorsolateral prefrontal cortex (dlPFC) in aging, schizophrenia and Alzheimer's disease. The current study compared glutamate and neuromodulatory actions in macaque V1 to those in dlPFC, and found striking regional differences. V1 neuronal firing to visual stimuli depended on AMPA receptors, with subtle NMDA receptor contributions, while dlPFC depends primarily on NMDA receptors. Neuromodulatory actions also differed between regions. In V1, cAMP signaling increased neuronal firing, and the phosphodiesterase PDE4A was positioned to regulate cAMP effects on glutamate release from axons...
January 17, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29346754/input-specific-nmdar-dependent-potentiation-of-dendritic-gabaergic-inhibition
#3
Chiayu Q Chiu, James S Martenson, Maya Yamazaki, Rie Natsume, Kenji Sakimura, Susumu Tomita, Steven J Tavalin, Michael J Higley
Preservation of a balance between synaptic excitation and inhibition is critical for normal brain function. A number of homeostatic cellular mechanisms have been suggested to play a role in maintaining this balance, including long-term plasticity of GABAergic inhibitory synapses. Many previous studies have demonstrated a coupling of postsynaptic spiking with modification of perisomatic inhibition. Here, we demonstrate that activation of NMDA-type glutamate receptors leads to input-specific long-term potentiation of dendritic inhibition mediated by somatostatin-expressing interneurons...
January 17, 2018: Neuron
https://www.readbyqxmd.com/read/29339791/the-glun2a-subunit-regulates-neuronal-nmda-receptor-induced-microglia-neuron-physical-interactions
#4
Ukpong B Eyo, Ashley Bispo, Junting Liu, Sruchika Sabu, Rong Wu, Victoria L DiBona, Jiaying Zheng, Madhuvika Murugan, Huaye Zhang, Yamei Tang, Long-Jun Wu
Microglia are known to engage in physical interactions with neurons. However, our understanding of the detailed mechanistic regulation of microglia-neuron interactions is incomplete. Here, using high resolution two photon imaging, we investigated the regulation of NMDA receptor-induced microglia-neuron physical interactions. We found that the GluN2A inhibitor NVPAAM007, but not the GluN2B inhibitor ifenprodil, blocked the occurrence of these interactions. Consistent with the well-known developmental regulation of the GluN2A subunit, these interactions are absent in neonatal tissues...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339535/functional-changes-of-ampa-responses-in-human-induced-pluripotent-stem-cell-derived-neural-progenitors-in-fragile-x-syndrome
#5
Venkat Swaroop Achuta, Tommi Möykkynen, Ulla-Kaisa Peteri, Giorgio Turconi, Claudio Rivera, Kari Keinänen, Maija L Castrén
Altered neuronal network formation and function involving dysregulated excitatory and inhibitory circuits are associated with fragile X syndrome (FXS). We examined functional maturation of the excitatory transmission system in FXS by investigating the response of FXS patient-derived neural progenitor cells to the glutamate analog (AMPA). Neural progenitors derived from induced pluripotent stem cell (iPSC) lines generated from boys with FXS had augmented intracellular Ca2+ responses to AMPA and kainate that were mediated by Ca2+-permeable AMPA receptors (CP-AMPARs) lacking the GluA2 subunit...
January 16, 2018: Science Signaling
https://www.readbyqxmd.com/read/29339324/oscillatory-synchronous-inhibition-in-the-basolateral-amygdala-and-its-primary-dependence-on-nr2a-containing-nmda-receptors
#6
Vassiliki Aroniadou-Anderjaska, Volodymyr I Pidoplichko, Taiza H Figueiredo, Maria F M Braga
Synchronous, rhythmic firing of GABAergic interneurons is a fundamental mechanism underlying the generation of brain oscillations, and evidence suggests that NMDA receptors (NMDARs) play a key role in oscillatory activity by regulating the activity of interneurons. Consistent with this, derangement of brain rhythms in certain neuropsychiatric disorders, notably schizophrenia and autism, is associated with NMDAR hypofunction and loss of inhibitory interneurons. In the basolateral amygdala (BLA)-dysfunction of which is involved in a host of neuropsychiatric diseases-, principal neurons display spontaneous, rhythmic "bursts" of inhibitory activity, which could potentially be involved in the orchestration of oscillations in the BLA network; here, we investigated the role of NMDARs in these inhibitory oscillations...
January 12, 2018: Neuroscience
https://www.readbyqxmd.com/read/29339173/neuroprotective-effects-of-topiramate-and-memantine-in-combination-with-hypothermia-in-hypoxic-ischemic-brain-injury-in-vitro-and-in-vivo
#7
Elisa Landucci, Luca Filippi, Elisabetta Gerace, Serena Catarzi, Renzo Guerrini, Domenico E Pellegrini-Giampietro
Hypoxic-ischemic encephalopathy (HIE) is a major cause of perinatal mortality and subsequent severe neurological sequelae. Mild hypothermia is a standard therapy for HIE, but is used only in selected Reference Centers and in neonates >1800 g. Since neuronal death following HIE occurs by a cascade of events triggered by activation of glutamate receptors, we used in vitro and in vivo models of HIE to examine whether the AMPA/kainate receptor antagonist topiramate and the NMDA receptor antagonist memantine could exert neuroprotective effects, alone or in combination with hypothermia...
January 12, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29339088/retinal-neuronal-cell-loss-prevents-abnormal-retinal-vascular-growth-in-a-rat-model-of-retinopathy-of-prematurity
#8
Ayuki Nakano, Daiki Asano, Ryo Kondo, Asami Mori, Shiho Arima, Hiroko Ushikubo, Kenji Sakamoto, Tohru Nagamitsu, Kunio Ishii, Tsutomu Nakahara
A short-term blockade of the vascular endothelial growth factor (VEGF)-mediated pathway in neonatal rats results in formation of severe retinopathy of prematurity (ROP)-like retinal blood vessels. The present study aimed to examine the role of retinal neurons in the formation of abnormal retinal blood vessels. Newborn rats were treated subcutaneously with the VEGF receptor tyrosine kinase inhibitor, KRN633 (10 mg/kg), or its vehicle (0.5% methylcellulose in water) on postnatal day (P) 7 and P8. To induce excitotoxic loss of retinal neurons, N-methyl-D-aspartic acid (NMDA) was injected into the vitreous chamber of the eye on P9...
January 12, 2018: Experimental Eye Research
https://www.readbyqxmd.com/read/29332578/amyloid-%C3%AE-inhibits-pdgf%C3%AE-receptor-activation-and-prevents-pdgf-bb-induced-neuroprotection
#9
Hui Liu, Golam T Saffi, Maryam S Vasefi, Youngjik Choi, Jeff S Kruk, Nawaz Ahmed, Nyasha Gondora, John Mielke, Zoya Leonenko, Michael A Beazely
PDGFβ receptors and their ligand, PDGF-BB, are upregulated in vivo after neuronal insults such as ischemia. When applied exogenously, PDGF-BB is neuroprotective against excitotoxicity and HIV proteins. METHODS: Given this growth factor's neuroprotective ability, we sought to determine if PDGF-BB would be neuroprotective against amyloid-β (1-42), one of the pathological agents associated with Alzheimer's disease (AD). In both primary hippocampal neurons and the human-derived neuroblastoma cell line, SH-SY5Y, amyloid- treatment for 24 h decreased surviving cell number in a concentration-dependent manner...
January 9, 2018: Current Alzheimer Research
https://www.readbyqxmd.com/read/29329983/attenuation-of-noise-induced-hyperactivity-in-the-dorsal-cochlear-nucleus-by-pre-treatment-with-mk-801
#10
M W Criddle, D A Godfrey, J A Kaltenbach
It has previously been hypothesized that hyperactivity of central auditory neurons following exposure to intense noise is a consequence of synaptic alterations. Recent studies suggest the involvement of NMDA receptors in the induction of this hyperactive state. NMDA receptors can mediate long term changes in the excitability of neurons through their involvement in excitotoxic injury and long term potentiation and depression. In this study, we examined the effect of administering an NMDA receptor blocker on the induction of hyperactivity in the dorsal cochlear nucleus (DCN) following intense sound exposure...
January 9, 2018: Brain Research
https://www.readbyqxmd.com/read/29325386/-the-protective-effect-of-the-activation-of-nmdar1-erk1-2-signal-pathway-induced-by-levodopa-on-visual-cortical-neurons-in-monocular-deprivation-rats
#11
X N Sun, H L Wang, G Qiao, J Tao, C Liu, X H Hao
Objective: To investigate the protection effects of the activation of NMDAR1(NMDA receptor 1)/ERK1/2 signal pathway on visual cortex nerve cells induced by levodopa in amblyopia rats. Methods: SD rats of SPF grade, were randomly divided into for groups of 9, group A. Control, B. MD group, C. L-levodopa(20 mg·kg(-1))+MD group, D. H-levodopa (80 mg·kg(-1))+MD group, E. H-levodopa+MD+MK801 group, F. H-levodopa+MD+PD98059 group, G. MD+MK801 group, H. MD+PD98059 group, I. MD+DMSO group. Amblyopia rats were made by suture of the right eye...
December 11, 2017: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
https://www.readbyqxmd.com/read/29325119/mir-96-is-required-for-normal-development-of-the-auditory-hindbrain
#12
Tina Schlüter, Christina Berger, Elena Rosengauer, Pascal Fieth, Constanze Krohs, Kathy Ushakov, Karen P Steel, Karen B Avraham, Alexander Hartmann, Felix Felmy, Hans Gerd Nothwang
The peripheral deafness gene Mir96 is expressed in both the cochlea and central auditory circuits. To investigate whether it plays a role in the auditory system beyond the cochlea, we characterized homozygous Dmdo/Dmdo mice with a point mutation in miR-96. Anatomical analysis demonstrated a significant decrease in volume of auditory nuclei in Dmdo/Dmdo mice. This decrease resulted from decreased cell size. Non-auditory structures in the brainstem of Dmdo/Dmdo mice or auditory nuclei of the congenital deaf Cldn14-/- mice revealed no such differences...
January 9, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29318854/-effect-of-electroacupuncture-on-intracellular-calcium-ion-concentration-and-expression-of-calcium-calmodulin-dependent-protein-kinase-%C3%A2-in-lumbar-spinal-cord-in-rats-with-neuropathic-pain
#13
Xin-Tian Wu, Wei Liang, Li-Ping Yan, Ling-Ling Wang, Cheng Ma
OBJECTIVE: To observe the changes of intracellular calcium ([Ca2+]i) concentration and expression of calcium/calmodulin dependent protein kinaseⅡ (CaMKⅡ) in spinal dorsal horn neurons of spared nerve injury (SNI) rats, so as to explore its mechanisms underlying improvement of neuropathic pain. METHODS: One hundred and ten SD rats were randomly divided into 5 groups: sham control, model, EA, AP-5 and L-NAME groups. The sham group underwent only a simple separation of the sciatic nerve but without ligation and abscission...
December 25, 2017: Zhen Ci Yan Jiu, Acupuncture Research
https://www.readbyqxmd.com/read/29301872/prefrontal-cortico-striatal-disconnection-blocks-the-acquisition-of-goal-directed-action
#14
Genevra Hart, Laura A Bradfield, Bernard W Balleine
The acquisition of goal-directed action requires encoding the association between an action and its specific consequences or outcome. At a neural level, this encoding has been hypothesized to involve a prefrontal corticostriatal circuit involving the projection from the prelimbic cortex (PL) to the posterior dorsomedial striatum (pDMS); however, no direct evidence for this claim has been reported. In a series of experiments, we performed functional disconnection of this pathway using targeted lesions of the anterior corpus callosum to disrupt contralateral corticostriatal projections with asymmetrical lesions of the PL and/or pDMS to block plasticity in this circuit in rats...
January 4, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29297151/liver-x-receptor-agonist-gw3965-regulates-synaptic-function-upon-amyloid-beta-exposure-in-hippocampal-neurons
#15
C Báez-Becerra, F Filipello, A Sandoval-Hernández, H Arboleda, G Arboleda
Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by beta-amyloid (Aβ) accumulation and neurofibrillary tangles formation in the brain which are associated to synaptic deficits and dementia. Liver X receptor (LXR) agonists have been demonstrated to revert of pathologic and cognitive defects in murine models of AD through the regulation of Apolipoprotein E, ATP-Binding Cassette A1 (ABCA1), by dampening neuroinflammation and also by reducing the levels of amyloid-β (Aβ) accumulation in the brain...
January 3, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29289718/a-high-fat-high-sugar-western-diet-alters-dorsal-striatal-glutamate-opioid-and-dopamine-transmission-in-mice
#16
Brandon M Fritz, Braulio Muñoz, Fuqin Yin, Casey Bauchle, Brady K Atwood
Understanding neuroadaptations involved in obesity is critical for developing new approaches to treatment. Diet-induced neuroadaptations within the dorsal striatum have the capacity to drive excessive food seeking and consumption. Five week old C57BL/6J mice consumed a high-fat, high-sugar 'western diet' (WD) or a control 'standard diet' (SD) for 16 weeks. Weight gain, glucose tolerance, and insulin tolerance were measured to confirm an obese-like state. Following these 16 weeks, electrophysiological recordings were made from medium spiny neurons (MSNs) in the medial (DMS) and lateral (DLS) portions of dorsal striatum to evaluate diet effects on neuronal excitability and synaptic plasticity...
December 28, 2017: Neuroscience
https://www.readbyqxmd.com/read/29285738/developmental-changes-of-synaptic-and-extrasynaptic-nmda-receptor-expression-in-rat-cerebellar-neurons-in-vitro
#17
Dmitry A Sibarov, Yulia D Stepanenko, Ivan V Silantiev, Polina A Abushik, Tatiana V Karelina, Sergei M Antonov
Transient expression of different NMDA receptors (NMDARs) plays a role in development of the cerebellum. Whether similar processes undergo during neuronal differentiation in culture is not clearly understood. We studied NMDARs in cerebellar neurons in cultures of 7 and 21 days in vitro (DIV) using immunocytochemical and electrophysiological approaches. Whereas at 7 DIV, the vast majority of neurons were immunopositive for GluN2 subunits, further synaptoginesis was accompanied by the time-dependent loss of NMDARs...
December 28, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29284046/irsp53-accumulates-at-the-postsynaptic-density-under-excitatory-conditions
#18
Ayse Dosemeci, Amelia Burch, Hannah Loo, Dana Toy, Jung-Hwa Tao-Cheng
IRSp53 (BAIAP2) is an abundant protein at the postsynaptic density (PSD) that binds to major PSD scaffolds, PSD-95 and Shanks, as well as to F-actin. The distribution of IRSp53 at the PSD in cultured hippocampal neurons was examined under basal and excitatory conditions by immuno-electron microscopy. Under basal conditions, label for IRSp53 is concentrated at the PSD. Upon depolarization by application of a medium containing 90 mM K+, the intensity of IRSp53 label at the PSD increased by 36±7%. Application of NMDA (50 μM) yielded 53±1% increase in the intensity of IRSp53 label at the PSD compared to controls treated with APV, an NMDA antagonist...
2017: PloS One
https://www.readbyqxmd.com/read/29283047/is-it-all-said-for-nsaids-in-alzheimer-s-disease-role-of-mitochondrial-calcium-uptake
#19
Sara Sanz-Blasco, Maria Calvo-Rodríguez, Erica Caballero, Monica Garcia-Durillo, Lucía Nunez, Carlos Villalobos
Epidemiological data suggest that non-steroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer's disease (AD). Unfortunately, recent trials have failed in providing compelling evidence of neuroprotection. Discussion as to why NSAIDs effectivity is uncertain is ongoing. Possible explanations include the view that NSAIDs and other possible disease-modifying drugs should be provided before the patients develop symptoms of AD or cognitive decline. In addition, NSAID targets for neuroprotection are unclear...
December 27, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/29279380/atm-and-atr-play-complementary-roles-in-the-behavior-of-excitatory-and-inhibitory-vesicle-populations
#20
Aifang Cheng, Teng Zhao, Kai-Hei Tse, Hei-Man Chow, Yong Cui, Liwen Jiang, Shengwang Du, Michael M T Loy, Karl Herrup
ATM (ataxia-telangiectasia mutated) and ATR (ATM and Rad3-related) are large PI3 kinases whose human mutations result in complex syndromes that include a compromised DNA damage response (DDR) and prominent nervous system phenotypes. Both proteins are nuclear-localized in keeping with their DDR functions, yet both are also found in cytoplasm, including on neuronal synaptic vesicles. In ATM- or ATR-deficient neurons, spontaneous vesicle release is reduced, but a drop in ATM or ATR level also slows FM4-64 dye uptake...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
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